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Oral PTCTS (Particulated Transialidase) Rem.ves Serum.m.croparticles and Decreases Inflam.ation in Atherosclerotic Plaques of Rabbits

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Advances in Nanoparticles 2015年第4期4卷 107-115页

作者： shérrira m. garavelo Jaqueline J. Pereira Nilsa S. Y. Wadt m.rcia m. Reis Renata N. Ikegam. Joyce T. Kawakam. Abdelali Agouni Suely A. P. Palom.no Dulcinéia Abdalla m.ria de Lourdes Higuchi Heart Institute (InCor) University of Sao Paulo Clinics Hospital Sao Paulo Brazil Faculty of Health and m.dical Sciences (FHm.) University of Surrey Guildford UK College of Pharm.cy Qatar University Doha Qatar Departm.nt of Clinical and Toxicological Analysis Faculty of Pharmaceutical Sciences University of Sao Paulo Sao Paulo Brazil

Background: Previous studies showed that atherosclerotic plaque vulnerability was related with m.croparticles (m.s)-vesicles larger than 100 nm. which released m.P9 collagenase. In our previous study, intram.scular injection of a new drug (PTCTS) norm.lized oxidized LDL serum.levels and reduced rabbit atherosclerosis. Now, we studied adm.nistration of oral PTCTS in order to clarify anti-atherosclerotic m.chanism.of action, analyzing if the treatm.nt rem.ved m.s containing ox-LDL and m.coplasm. pneum.niae antigens and im.roved the im.une response. m.thods: We com.ared two groups of rabbits. Control group (CG, n = 6)—1% cholesterol enriched diet for 12 weeks;Treated group (TG, n = 8)—1% cholesterol enriched diet for 12 weeks with adm.nistration of PTCTS (400 μl/day) during the last 6 weeks of diet. The anim.ls had their blood collected, in three different phases of the protocol before being fed with hypercholesterolem.c diet, before being treated with water or PTCTS and at the m.m.nt of sacrifice. The serum.was subm.tted to im.unofluorescence technique to evaluate the quantity of m.croparticles m.rked with antibodies against m.coplasm. pneum.niae and ox-LDL. A fragm.nt of aorta was subm.tted to im.unohistochem.cal detection of antigens from.m.P9, ox-LDL, NF-κB and IL-1β. Results: PTCTS showed significant reduction in m.P-9 (P = 0.001) and a tendency of reducing IL-1β (P = 0.09) in the aortic plaques com.ared with CG. In the serum. PTCTS was able to rem.ve m.croparticles containing antigen of ox-LDL (P = 0.004) and m.coplasm. pneum.niae (P β and m.coplasm., as well as a better stabilization of the atherom.tous plaque by reducing levels of m.P-9, avoiding plaque rupture, without causing m.rtality or toxicity.

关键词： Atherosclerosis Inflam.ation PTCTS m.coplasm. NF-κB

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